We analyzed 39 autoimmune disease- and trait-associated SNP sets, obtained from the Supplemental table 1 of the Farh, K. K.-H., Marson, A., Zhu, J., Kleinewietfeld, M., Housley, W. J., Beik, S., … Bernstein, B. E. (2014). “Genetic and epigenetic fine mapping of causal autoimmune disease variants”“ Nature. doi:10.1038/nature13835.

First, we re-created the heatmap of shared genetic features among the autoimmune diseases and traits, that is, counts of genomic elements overlapping between pairs of terms. We will use this heatmap as a reference point to compare with the heatmaps produced by the regulatory similarity analysis.

Analysis of all regulatory datasets

Although we used 4,498 regulatory datasets from the ENCODE project processed with the use with GenomeRunner, some regulatory datasets show not statistically significant enrichments in any of the 39 SNP sets. We removed these datasets as non-informative, and kept the remaining 2,969 regulatory datasets.

## [1] 4498   39
## [1] 2969   39

We visualized the matrix of pair-wise pearson correlation coefficients among the term-specific regulatory enrichment profiles.

We then compared how regulatory similarity correlates with shared genomic features similarity. pearson correlation coefficient between the two is:

## [1] 0.6680046

The top 10 pairs of disease- aassociated SNPs are most similar with each other. The correlation coefficient shows pearson correlation coefficient among the regulatory enrichment profiles for each term-specific SNP set.

## 
## --------------------------------------------------------------------------
##         Disease 1                  Disease 2            Corr. coefficient 
## ------------------------- ---------------------------- -------------------
##    Multiple_sclerosis     Systemic_lupus_erythematosus       0.4557       
## 
##      Celiac_disease            Multiple_sclerosis            0.4392       
## 
##     Kawasaki_disease      Systemic_lupus_erythematosus       0.4383       
## 
## Primary_biliary_cirrhosis Systemic_lupus_erythematosus       0.3928       
## 
##      HDL_cholesterol            LDL_cholesterol               0.389       
## 
##      Platelet_counts             Triglycerides               0.3847       
## 
##   Rheumatoid_arthritis         Ulcerative_colitis            0.3566       
## 
##      HDL_cholesterol             Triglycerides               0.3503       
## 
##    Multiple_sclerosis      Primary_biliary_cirrhosis         0.3322       
## 
##      LDL_cholesterol             Triglycerides               0.2817       
## --------------------------------------------------------------------------

The regulatory similarity dendrogram can be divided into four separate clusters:

## Cluster01 has   5 members 
## Platelet_counts
## Triglycerides
## Liver_enzyme_levels_gamma_glutamyl_transferase
## LDL_cholesterol
## HDL_cholesterol
##  
## Cluster02 has  14 members 
## Bone_mineral_density
## Creatinine_levels
## Chronic_kidney_disease
## Urate_levels
## Vitiligo
## Type_2_diabetes
## Fasting_glucose_related_traits
## Alzheimers_combined
## Restless_legs_syndrome
## Ankylosing_spondylitis
## Primary_sclerosing_cholangitis
## Systemic_sclerosis
## Red_blood_cell_traits
## Migraine
##  
## Cluster03 has   5 members 
## Multiple_sclerosis
## Celiac_disease
## Primary_biliary_cirrhosis
## Systemic_lupus_erythematosus
## Kawasaki_disease
##  
## Cluster04 has  15 members 
## Type_1_diabetes
## Behcets_disease
## Juvenile_idiopathic_arthritis
## Renal_function_related_traits_BUN
## Asthma
## Allergy
## Progressive_supranuclear_palsy
## Psoriasis
## Autoimmune_thyroiditis
## Crohns_disease
## Rheumatoid_arthritis
## Ulcerative_colitis
## Alopecia_areata
## C_reactive_protein
## Atopic_dermatitis
## 

We estimated the differences in regulatory associations of term-secific SNP sets.

The first column shows names of regulatory datasets. The following two columns show the average p-values of the cluster-specific SNP sets-regulatory associations. The smaller a p-value is, the more SNPs in a cluster enriched in corresponsing regulatory dataset. A “-” sign indicates that an association is underrepresented (depleted). The “adj.P.Val” column shows whether a difference in the associations between the clusters is statistically significantly different. The last column shows descriptions of the regulatory datasets. The tables were sorted by “adj.P.Val” column; the top 10 or less most significantly different associations are shown.

## [1] "c1 vs. c2 , number of degs significant at adj.p.val<0.5: 38"
## 
## ---------------------------------------------------------------------------------------------------------------
##                      Row.names                         c1       c2     adj.P.Val               V2              
## --------------------------------------------------- --------- ------- ----------- -----------------------------
##         wgEncodeSydhTfbsK562Pol2Ifng30StdPk         0.006469  0.9072   0.001309   K562 Pol2 Standard IFNg 30min
##                                                                                        ChIP-seq Peaks from     
##                                                                                            ENCODE/SYDH         
## 
##       wgEncodeHaibTfbsHepg2P300V0416101PkRep2        0.00722  0.7239   0.001309   HepG2 p300 v041610.1 ChIP-seq
##                                                                                   Peaks Rep 2 from ENCODE/HAIB 
## 
##          wgEncodeOpenChromChipHepg2Pol2Pk           6.913e-07 -0.6861  0.002655     HepG2 Pol2 TFBS ChIP-seq   
##                                                                                            Peaks from          
##                                                                                       ENCODE/OpenChrom-UTA     
## 
##     wgEncodeHaibTfbsHepg2Pol24h8V0416102PkRep2      8.983e-07 -0.5865  0.007927     HepG2 Pol2-4H8 v041610.2   
##                                                                                     ChIP-seq Peaks Rep 2 from  
##                                                                                            ENCODE/HAIB         
## 
##     wgEncodeGisRnaPetNhekNucleusPapClustersRep1     8.839e-05 0.9334   0.008137        NHEK nucleus polyA+     
##                                                                                    clone-free RNA PET Clusters 
##                                                                                       Rep 1 from ENCODE/GIS    
## 
## wgEncodeUwHistoneH7esH3k36me3StdDiffa5dHotspotsRep2 0.005028  0.8859   0.008137   H7-hESC H3K36me3 diffProtA 5 
##                                                                                      d Histone Mod ChIP-seq    
##                                                                                     Hotspots 2 from ENCODE/UW  
## 
##         wgEncodeBroadHistoneNhekH3k79me2Pk           1.5e-05  -0.5031  0.008137   NHEK H3K79me2 Histone Mods by
##                                                                                        ChIP-seq Peaks from     
##                                                                                           ENCODE/Broad         
## 
##   wgEncodeHaibTfbsHepg2Mybl2sc81192V0422111PkRep1   0.005722  0.9924   0.008363       HepG2 MYBL2 v042211.1    
##                                                                                     ChIP-seq Peaks Rep 1 from  
##                                                                                            ENCODE/HAIB         
## 
##          wgEncodeSydhTfbsHepg2Pol2IggrabPk          0.0003379 -0.7955  0.008975    HEPG2 Pol2 IgG-rab ChIP-seq 
##                                                                                      Peaks from ENCODE/SYDH    
## 
##        wgEncodeHaibTfbsHepg2Pol2Pcr2xPkRep2         0.001453  -0.8593   0.01037     HepG2 Pol2 PCR2x ChIP-seq  
##                                                                                   Peaks Rep 2 from ENCODE/HAIB 
## ---------------------------------------------------------------------------------------------------------------
## 
## [1] "c1 vs. c3 , number of degs significant at adj.p.val<0.5: 172"
## 
## ------------------------------------------------------------------------------------------------------------
##                    Row.names                        c1       c3      adj.P.Val               V2             
## ------------------------------------------------ -------- --------- ----------- ----------------------------
##         wgEncodeOpenChromFaireGm19239Pk          -0.08204 0.0001051  1.38e-09     GM19239 FAIRE Peaks from  
##                                                                                    ENCODE/OpenChrom(UNC)    
## 
## wgEncodeHaibTfbsGm12878Nficsc81335V0422111PkRep2 -0.1304  0.002245   6.733e-08     GM12878 NFIC v042211.1   
##                                                                                  ChIP-seq Peaks Rep 2 from  
##                                                                                         ENCODE/HAIB         
## 
## wgEncodeHaibTfbsGm12878Nficsc81335V0422111PkRep1 -0.05001 2.709e-06  2.289e-07     GM12878 NFIC v042211.1   
##                                                                                  ChIP-seq Peaks Rep 1 from  
##                                                                                         ENCODE/HAIB         
## 
##         wgEncodeOpenChromSynthGm18507Pk          -0.4051  0.0004778  6.783e-07   GM18507 DNaseI/FAIRE/ChIP  
##                                                                                        Synthesis from       
##                                                                                       ENCODE/OpenChrom      
## 
##         wgEncodeOpenChromFaireGm18507Pk          -0.3038  4.213e-05  8.87e-06     GM18507 FAIRE Peaks from  
##                                                                                    ENCODE/OpenChrom(UNC)    
## 
##        wgEncodeUwDnaseGm12865HotspotsRep2        -0.3793  8.456e-06  1.22e-05    GM12865 DNaseI HS HotSpots 
##                                                                                     Rep 2 from ENCODE/UW    
## 
##     wgEncodeBroadHistoneGm12878H3k4me2StdPk      -0.06231 9.346e-10  1.237e-05  GM12878 H3K4me2 Histone Mods
##                                                                                    by ChIP-seq Peaks from   
##                                                                                         ENCODE/Broad        
## 
##        wgEncodeBroadHistoneDnd41H3k09acPk        -0.6002  2.678e-05  1.298e-05  Dnd41 H3K9ac Histone Mods by
##                                                                                     ChIP-seq Peaks from     
##                                                                                         ENCODE/Broad        
## 
##        wgEncodeUwDnaseGm12865HotspotsRep1        -0.2387  8.471e-05  2.134e-05   GM12865 DNaseI HS HotSpots 
##                                                                                     Rep 1 from ENCODE/UW    
## 
##      wgEncodeBroadHistoneGm12878H3k9acStdPk      -0.05389 5.217e-13  2.851e-05  GM12878 H3K9ac Histone Mods 
##                                                                                    by ChIP-seq Peaks from   
##                                                                                         ENCODE/Broad        
## ------------------------------------------------------------------------------------------------------------
## 
## [1] "c1 vs. c4 , number of degs significant at adj.p.val<0.5: 85"
## 
## -----------------------------------------------------------------------------------------------------------------
##                      Row.names                          c1        c4     adj.P.Val               V2              
## --------------------------------------------------- ---------- -------- ----------- -----------------------------
##       wgEncodeHaibTfbsHepg2P300V0416101PkRep2        0.00722    0.9498   0.0007524  HepG2 p300 v041610.1 ChIP-seq
##                                                                                     Peaks Rep 2 from ENCODE/HAIB 
## 
##         wgEncodeSydhTfbsK562Pol2Ifng30StdPk          0.006469   0.6275   0.001175   K562 Pol2 Standard IFNg 30min
##                                                                                          ChIP-seq Peaks from     
##                                                                                              ENCODE/SYDH         
## 
## wgEncodeUwHistoneH7esH3k36me3StdDiffa5dHotspotsRep2  0.005028  -0.4649   0.001175   H7-hESC H3K36me3 diffProtA 5 
##                                                                                        d Histone Mod ChIP-seq    
##                                                                                       Hotspots 2 from ENCODE/UW  
## 
##    wgEncodeGisRnaPetHepg2CytosolPapClustersRep1     6.141e-06  -0.01792  0.001175       HepG2 cytosol polyA+     
##                                                                                     clone-based RNA PET Clusters 
##                                                                                         Rep 1 from ENCODE/GIS    
## 
##     wgEncodeGisRnaPetNhekNucleusPapClustersRep1     8.839e-05  -0.2856   0.001175        NHEK nucleus polyA+     
##                                                                                      clone-free RNA PET Clusters 
##                                                                                         Rep 1 from ENCODE/GIS    
## 
##          wgEncodeOpenChromChipHepg2Pol2Pk           6.913e-07  -0.6948   0.001175     HepG2 Pol2 TFBS ChIP-seq   
##                                                                                              Peaks from          
##                                                                                         ENCODE/OpenChrom-UTA     
## 
##         wgEncodeBroadHistoneHuvecH3k79me2Pk          2.13e-05   -0.106   0.001175    HUVEC H3K79me2 Histone Mods 
##                                                                                        by ChIP-seq Peaks from    
##                                                                                             ENCODE/Broad         
## 
##         wgEncodeBroadHistoneNhekH3k79me2Pk           1.5e-05   -0.1112   0.001309   NHEK H3K79me2 Histone Mods by
##                                                                                          ChIP-seq Peaks from     
##                                                                                             ENCODE/Broad         
## 
##    wgEncodeGisRnaPetHepg2NucleusPapClustersRep1     6.638e-06  -0.02357  0.002597       HepG2 nucleus polyA+     
##                                                                                     clone-based RNA PET Clusters 
##                                                                                         Rep 1 from ENCODE/GIS    
## 
##       wgEncodeBroadHistoneHuvecH3k27me3StdPk        -4.101e-05  0.1422   0.003049    HUVEC H3K27me3 Histone Mods 
##                                                                                        by ChIP-seq Peaks from    
##                                                                                             ENCODE/Broad         
## -----------------------------------------------------------------------------------------------------------------
## 
## [1] "c2 vs. c3 , number of degs significant at adj.p.val<0.5: 159"
## 
## -------------------------------------------------------------------------------------------------------------
##                    Row.names                        c2       c3      adj.P.Val               V2              
## ------------------------------------------------ -------- --------- ----------- -----------------------------
##         wgEncodeOpenChromFaireGm19239Pk          -0.3865  0.0001051  3.218e-10    GM19239 FAIRE Peaks from   
##                                                                                     ENCODE/OpenChrom(UNC)    
## 
##         wgEncodeOpenChromSynthGm18507Pk           -0.566  0.0004778  2.006e-08    GM18507 DNaseI/FAIRE/ChIP  
##                                                                                        Synthesis from        
##                                                                                       ENCODE/OpenChrom       
## 
## wgEncodeHaibTfbsGm12878Nficsc81335V0422111PkRep1 -0.2202  2.709e-06  2.006e-08     GM12878 NFIC v042211.1    
##                                                                                   ChIP-seq Peaks Rep 1 from  
##                                                                                          ENCODE/HAIB         
## 
## wgEncodeHaibTfbsGm12878Nficsc81335V0422111PkRep2  -0.517  0.002245   2.708e-08     GM12878 NFIC v042211.1    
##                                                                                   ChIP-seq Peaks Rep 2 from  
##                                                                                          ENCODE/HAIB         
## 
##     wgEncodeBroadHistoneGm12878H3k4me2StdPk      -0.02211 9.346e-10  8.134e-08  GM12878 H3K4me2 Histone Mods 
##                                                                                    by ChIP-seq Peaks from    
##                                                                                         ENCODE/Broad         
## 
##        wgEncodeUwDnaseGm12865HotspotsRep2        -0.2974  8.456e-06  1.038e-07   GM12865 DNaseI HS HotSpots  
##                                                                                     Rep 2 from ENCODE/UW     
## 
##        wgEncodeBroadHistoneDnd41H3k09acPk        -0.4638  2.678e-05  1.161e-07  Dnd41 H3K9ac Histone Mods by 
##                                                                                      ChIP-seq Peaks from     
##                                                                                         ENCODE/Broad         
## 
##         wgEncodeOpenChromFaireGm18507Pk          -0.4293  4.213e-05  1.561e-07    GM18507 FAIRE Peaks from   
##                                                                                     ENCODE/OpenChrom(UNC)    
## 
##       wgEncodeBroadHistoneDnd41H3k04me1Pk        -0.1887  3.207e-09  2.345e-07  Dnd41 H3K4me1 Histone Mods by
##                                                                                      ChIP-seq Peaks from     
##                                                                                         ENCODE/Broad         
## 
##      wgEncodeSydhTfbsGm12878Pol2s2IggmusPk        -0.24   5.349e-06  3.092e-07     GM12878 Pol2 S2 IgG-mus   
##                                                                                      ChIP-seq Peaks from     
##                                                                                          ENCODE/SYDH         
## -------------------------------------------------------------------------------------------------------------
## 
## [1] "c3 vs. c4 , number of degs significant at adj.p.val<0.5: 152"
## 
## ------------------------------------------------------------------------------------------------------------
##                    Row.names                        c3       c4     adj.P.Val               V2              
## ------------------------------------------------ --------- ------- ----------- -----------------------------
##         wgEncodeOpenChromFaireGm19239Pk          0.0001051 0.6658   1.398e-08    GM19239 FAIRE Peaks from   
##                                                                                    ENCODE/OpenChrom(UNC)    
## 
##         wgEncodeOpenChromSynthGm18507Pk          0.0004778 0.6495   6.122e-07    GM18507 DNaseI/FAIRE/ChIP  
##                                                                                       Synthesis from        
##                                                                                      ENCODE/OpenChrom       
## 
##        wgEncodeBroadHistoneDnd41H3k09acPk        2.678e-05 -0.8745  8.889e-07  Dnd41 H3K9ac Histone Mods by 
##                                                                                     ChIP-seq Peaks from     
##                                                                                        ENCODE/Broad         
## 
##       wgEncodeBroadHistoneDnd41H3k04me1Pk        3.207e-09 -0.7861  2.207e-06  Dnd41 H3K4me1 Histone Mods by
##                                                                                     ChIP-seq Peaks from     
##                                                                                        ENCODE/Broad         
## 
## wgEncodeHaibTfbsGm12878Nficsc81335V0422111PkRep1 2.709e-06 0.2551   2.391e-06     GM12878 NFIC v042211.1    
##                                                                                  ChIP-seq Peaks Rep 1 from  
##                                                                                         ENCODE/HAIB         
## 
##         wgEncodeOpenChromFaireGm18507Pk          4.213e-05 0.6812   2.798e-06    GM18507 FAIRE Peaks from   
##                                                                                    ENCODE/OpenChrom(UNC)    
## 
##        wgEncodeUwDnaseGm12865HotspotsRep2        8.456e-06 0.5282   2.825e-06   GM12865 DNaseI HS HotSpots  
##                                                                                    Rep 2 from ENCODE/UW     
## 
## wgEncodeHaibTfbsGm12878Nficsc81335V0422111PkRep2 0.002245  0.4559   3.584e-06     GM12878 NFIC v042211.1    
##                                                                                  ChIP-seq Peaks Rep 2 from  
##                                                                                         ENCODE/HAIB         
## 
##     wgEncodeBroadHistoneGm12878H3k4me2StdPk      9.346e-10 0.3976   5.523e-06  GM12878 H3K4me2 Histone Mods 
##                                                                                   by ChIP-seq Peaks from    
##                                                                                        ENCODE/Broad         
## 
##   wgEncodeSydhTfbsGm12878Chd1a301218aIggmusPk    1.229e-06 0.7272   7.359e-06  GM12878 CHD1 IgG-mus ChIP-seq
##                                                                                   Peaks from ENCODE/SYDH    
## ------------------------------------------------------------------------------------------------------------
## [1] "Counts of regulatory elements differentially associated with each group"
## 
## ----------------------------
##  &nbsp;   c1   c2   c3   c4 
## -------- ---- ---- ---- ----
##  **c1**   0    38  172   85 
## 
##  **c2**   0    0   159   0  
## 
##  **c3**   0    0    0   152 
## 
##  **c4**   0    0    0    0  
## ----------------------------

Summary

The differences in regulatory associations are attributed to the clusters 1 and 3.

The cluster 1 (Platelet_counts, Triglycerides, Liver_enzyme_levels_gamma_glutamyl_transferase, LDL_cholesterol, HDL_cholesterol) showed enrichment in PolII, H3K36me3 and H3K79me2 histone modification marks. The signals was derived predominantly from cancer-related cell lines, such as HepG2 (liver hepatocellular carcinoma), K562 (myelogeneous leukemia), A549 (adenocarcinomic human alveolar basal epithelial cells).

The cluster 3 (Multiple_sclerosis, Celiac_disease, Primary_biliary_cirrhosis, Systemic_lupus_erythematosus, Kawasaki_disease) showed strong enrichment in B-cell derived signal. The most predominant cell type was Gm12878 (B lymphoblastoid cell line), CD20+ B cells, although some signal came from Dnd41 cells (T-ALL), T helper cells 1 and 2, and CD14+ monocytes. DNAse hypersensitive sites were predominant type of signal enriched in the disease-associated SNPs from this cluster, followed by H3K4 mono-/di- and trimethylation, PolII, H3K79me2, H3K27 trimethylation and acetylation, and the CTCF, NFkB, NFATC1, STAT5A and other transcription factor binding sites

Co-morbidity similarity analysis

We used the data from Hidalgo CA, Blumm N, Barabasi A-L, Christakis NA. PLoS Computational Biology, 5(4):e1000353 doi:10.1371/journal.pcbi.1000353, available at http://barabasilab.neu.edu/projects/hudine/resource/data/data.html. These data provide co-morbidity measurements among pairs of diseases. We map autoimmune disease- and trait names to 3-digits ICD9 codes and evaluate how co-morbidity measurements correlate with regulatory similarity measurements. We used Phi measurement of co-morbidity. The pearson correlation coefficient of Phi and regulatory similarity is:

## [1] 0.4011363

Iridescent literature similarity

## [1] "sharedRels correlation with regulatory similarity"
## [1] 0.3657238
## [1] "obsExp correlation with regulatory similarity"
## [1] 0.5619774
## [1] "minMim correlation with regulatory similarity"
## [1] 0.7311888
## [1] "directStr correlation with regulatory similarity"
## [1] 0.1968273
## [1] "relOverlap correlation with regulatory similarity"
## [1] 0.3851007
## [1] "misn correlation with regulatory similarity"
## [1] 0.7310631

UMLS literature similarity

## [1] "msh.path correlation with regulatory similarity"
## [1] 0.3092355
## [1] "snomedct.path correlation with regulatory similarity"
## [1] 0.8287126

Analysis of TFBSs

We also performed regulatory similarity analysis using subsets of regulatory datasets, such as Transcription Factor Binding Sites or Histone Modification Marks. Here, out of all regulatory datasets, we selected only TFBSs.

## [1] 1954   39
## [1] 1259   39

We visualized the matrix of pair-wise pearson correlation coefficients among the term-specific regulatory enrichment profiles.

We then compared how regulatory similarity correlates with shared genomic features similarity. pearson correlation coefficient between the two is:

## [1] 0.6298022

The top 10 pairs of disease-associated SNPs are most similar with each other.

## 
## -----------------------------------------------------------------------
##       Disease 1                 Disease 2            Corr. coefficient 
## ---------------------- ---------------------------- -------------------
##    Kawasaki_disease    Systemic_lupus_erythematosus       0.7189       
## 
##    HDL_cholesterol           LDL_cholesterol              0.6883       
## 
##   Multiple_sclerosis   Systemic_lupus_erythematosus       0.6683       
## 
## Ankylosing_spondylitis        Crohns_disease              0.6548       
## 
##  Bone_mineral_density        Type_2_diabetes               0.584       
## 
##    HDL_cholesterol            Triglycerides               0.5278       
## 
## Ankylosing_spondylitis      Ulcerative_colitis            0.5021       
## 
##    Kawasaki_disease        Rheumatoid_arthritis           0.4912       
## 
##  Alzheimers_combined         Type_2_diabetes              0.4884       
## 
##    Kawasaki_disease         Multiple_sclerosis            0.4872       
## -----------------------------------------------------------------------

The regulatory similarity dendrogram can be divided into four separate clusters:

## Cluster01 has   6 members 
## Multiple_sclerosis
## Systemic_lupus_erythematosus
## Kawasaki_disease
## Psoriasis
## Celiac_disease
## Ulcerative_colitis
##  
## Cluster02 has   6 members 
## Allergy
## Rheumatoid_arthritis
## Autoimmune_thyroiditis
## Primary_biliary_cirrhosis
## Migraine
## Systemic_sclerosis
##  
## Cluster03 has   4 members 
## Chronic_kidney_disease
## Type_2_diabetes
## Bone_mineral_density
## Alzheimers_combined
##  
## Cluster04 has   5 members 
## Urate_levels
## Liver_enzyme_levels_gamma_glutamyl_transferase
## Triglycerides
## HDL_cholesterol
## LDL_cholesterol
##  
## Cluster05 has   2 members 
## Crohns_disease
## Ankylosing_spondylitis
##  
## Cluster06 has  16 members 
## Renal_function_related_traits_BUN
## Fasting_glucose_related_traits
## Platelet_counts
## Juvenile_idiopathic_arthritis
## Atopic_dermatitis
## Red_blood_cell_traits
## C_reactive_protein
## Primary_sclerosing_cholangitis
## Alopecia_areata
## Asthma
## Behcets_disease
## Progressive_supranuclear_palsy
## Creatinine_levels
## Restless_legs_syndrome
## Type_1_diabetes
## Vitiligo
## 

We estimated the differences in regulatory associations of term-secific SNP sets.

The first column shows names of regulatory datasets. The following two columns show the average p-values of the cluster-specific SNP sets-regulatory associations. The smaller a p-value is, the more SNPs in a cluster enriched in corresponsing regulatory dataset. A “-” sign indicates that an association is underrepresented (depleted). The “adj.P.Val” column shows whether a difference in the associations between the clusters is statistically significantly different. The last column shows descriptions of the regulatory datasets. The tables were sorted by “adj.P.Val” column; the top 10 or less most significantly different associations are shown.

## [1] "c1 vs. c2 , number of degs significant at adj.p.val<0.5: 62"
## 
## -------------------------------------------------------------------------------------------------------------
##                     Row.names                         c1       c2    adj.P.Val               V2              
## -------------------------------------------------- --------- ------ ----------- -----------------------------
## wgEncodeHaibTfbsGm12878Runx3sc101553V0422111PkRep2 8.939e-05 0.561   3.281e-09     GM12878 RUNX3 v042211.1   
##                                                                                   ChIP-seq Peaks Rep 2 from  
##                                                                                          ENCODE/HAIB         
## 
##  wgEncodeHaibTfbsGm12878Pmlsc71910V0422111PkRep2   1.027e-05 0.507   3.952e-09      GM12878 PML v042211.1    
##                                                                                   ChIP-seq Peaks Rep 2 from  
##                                                                                          ENCODE/HAIB         
## 
## wgEncodeHaibTfbsGm12878Stat5asc74442V0422111PkRep2 5.806e-05 0.8614  5.249e-09    GM12878 STAT5A v042211.1   
##                                                                                   ChIP-seq Peaks Rep 2 from  
##                                                                                          ENCODE/HAIB         
## 
##      wgEncodeHaibTfbsGm12878Pou2f2Pcr1xPkRep2      0.003845  0.9554  1.375e-07  GM12878 POU2F2 PCR1x ChIP-seq
##                                                                                 Peaks Rep 2 from ENCODE/HAIB 
## 
##       wgEncodeHaibTfbsGm12891Pol2Pcr1xPkRep1       0.004814  0.6935  2.882e-07   GM12891 Pol2 PCR1x ChIP-seq 
##                                                                                 Peaks Rep 1 from ENCODE/HAIB 
## 
## wgEncodeHaibTfbsGm12878Stat5asc74442V0422111PkRep1 0.000687  0.906   2.89e-07     GM12878 STAT5A v042211.1   
##                                                                                   ChIP-seq Peaks Rep 1 from  
##                                                                                          ENCODE/HAIB         
## 
##  wgEncodeHaibTfbsGm12878Bclaf101388V0416101PkRep2  0.001796  0.4804  5.46e-07     GM12878 BCLAF1 v041610.1   
##                                                                                   ChIP-seq Peaks Rep 2 from  
##                                                                                          ENCODE/HAIB         
## 
##       wgEncodeHaibTfbsGm12878Pol2Pcr2xPkRep1       0.0001325 0.6133  5.46e-07    GM12878 Pol2 PCR2x ChIP-seq 
##                                                                                 Peaks Rep 1 from ENCODE/HAIB 
## 
##  wgEncodeHaibTfbsGm12878Mta3sc81325V0422111PkRep2  7.449e-07 0.4086  5.46e-07      GM12878 MTA3 v042211.1    
##                                                                                   ChIP-seq Peaks Rep 2 from  
##                                                                                          ENCODE/HAIB         
## 
##  wgEncodeHaibTfbsGm12878Atf2sc81188V0422111PkRep1  0.0001343 0.5215  4.325e-06     GM12878 ATF2 v042211.1    
##                                                                                   ChIP-seq Peaks Rep 1 from  
##                                                                                          ENCODE/HAIB         
## -------------------------------------------------------------------------------------------------------------
## 
## [1] "c1 vs. c3 , number of degs significant at adj.p.val<0.5: 65"
## 
## -----------------------------------------------------------------------------------------------------------------
##                     Row.names                         c1         c3      adj.P.Val               V2              
## -------------------------------------------------- --------- ---------- ----------- -----------------------------
##  wgEncodeHaibTfbsGm12878Pmlsc71910V0422111PkRep2   1.027e-05  -0.01199   3.087e-12      GM12878 PML v042211.1    
##                                                                                       ChIP-seq Peaks Rep 2 from  
##                                                                                              ENCODE/HAIB         
## 
## wgEncodeHaibTfbsGm12878Runx3sc101553V0422111PkRep2 8.939e-05  -0.07637   1.033e-11     GM12878 RUNX3 v042211.1   
##                                                                                       ChIP-seq Peaks Rep 2 from  
##                                                                                              ENCODE/HAIB         
## 
## wgEncodeHaibTfbsGm12878Stat5asc74442V0422111PkRep2 5.806e-05  -0.02658   1.402e-11    GM12878 STAT5A v042211.1   
##                                                                                       ChIP-seq Peaks Rep 2 from  
##                                                                                              ENCODE/HAIB         
## 
##       wgEncodeHaibTfbsGm12878Pol2Pcr2xPkRep1       0.0001325  -0.01003   1.366e-10   GM12878 Pol2 PCR2x ChIP-seq 
##                                                                                     Peaks Rep 1 from ENCODE/HAIB 
## 
##  wgEncodeHaibTfbsGm12878Mta3sc81325V0422111PkRep2  7.449e-07 -0.0008688  1.366e-10     GM12878 MTA3 v042211.1    
##                                                                                       ChIP-seq Peaks Rep 2 from  
##                                                                                              ENCODE/HAIB         
## 
##      wgEncodeHaibTfbsGm12878Pou2f2Pcr1xPkRep2      0.003845   -0.09044   1.484e-10  GM12878 POU2F2 PCR1x ChIP-seq
##                                                                                     Peaks Rep 2 from ENCODE/HAIB 
## 
##       wgEncodeHaibTfbsGm12891Pol2Pcr1xPkRep1       0.004814   -0.2148    1.16e-09    GM12891 Pol2 PCR1x ChIP-seq 
##                                                                                     Peaks Rep 1 from ENCODE/HAIB 
## 
##  wgEncodeHaibTfbsGm12878Bclaf101388V0416101PkRep2  0.001796   -0.1952    1.91e-09     GM12878 BCLAF1 v041610.1   
##                                                                                       ChIP-seq Peaks Rep 2 from  
##                                                                                              ENCODE/HAIB         
## 
##  wgEncodeHaibTfbsGm12878Atf2sc81188V0422111PkRep2  0.0007129  -0.05776   1.951e-09     GM12878 ATF2 v042211.1    
##                                                                                       ChIP-seq Peaks Rep 2 from  
##                                                                                              ENCODE/HAIB         
## 
## wgEncodeHaibTfbsGm12878Runx3sc101553V0422111PkRep1 0.0001092  -0.01052   4.089e-09     GM12878 RUNX3 v042211.1   
##                                                                                       ChIP-seq Peaks Rep 1 from  
##                                                                                              ENCODE/HAIB         
## -----------------------------------------------------------------------------------------------------------------
## 
## [1] "c1 vs. c4 , number of degs significant at adj.p.val<0.5: 77"
## 
## ---------------------------------------------------------------------------------------------------------------
##                     Row.names                         c1        c4     adj.P.Val               V2              
## -------------------------------------------------- --------- -------- ----------- -----------------------------
## wgEncodeHaibTfbsGm12878Runx3sc101553V0422111PkRep2 8.939e-05 -0.1192   1.486e-11     GM12878 RUNX3 v042211.1   
##                                                                                     ChIP-seq Peaks Rep 2 from  
##                                                                                            ENCODE/HAIB         
## 
##  wgEncodeHaibTfbsGm12878Pmlsc71910V0422111PkRep2   1.027e-05 -0.1599   5.185e-11      GM12878 PML v042211.1    
##                                                                                     ChIP-seq Peaks Rep 2 from  
##                                                                                            ENCODE/HAIB         
## 
## wgEncodeHaibTfbsGm12878Stat5asc74442V0422111PkRep2 5.806e-05 -0.2564   3.98e-10     GM12878 STAT5A v042211.1   
##                                                                                     ChIP-seq Peaks Rep 2 from  
##                                                                                            ENCODE/HAIB         
## 
##  wgEncodeHaibTfbsGm12878Nficsc81335V0422111PkRep1  8.776e-06 -0.0344   1.617e-08     GM12878 NFIC v042211.1    
##                                                                                     ChIP-seq Peaks Rep 1 from  
##                                                                                            ENCODE/HAIB         
## 
##  wgEncodeHaibTfbsGm12878Foxm1sc502V0422111PkRep1   0.0002931 -0.09224  1.617e-08     GM12878 FOXM1 v042211.1   
##                                                                                     ChIP-seq Peaks Rep 1 from  
##                                                                                            ENCODE/HAIB         
## 
## wgEncodeHaibTfbsGm12878Stat5asc74442V0422111PkRep1 0.000687  -0.3028   1.617e-08    GM12878 STAT5A v042211.1   
##                                                                                     ChIP-seq Peaks Rep 1 from  
##                                                                                            ENCODE/HAIB         
## 
##  wgEncodeHaibTfbsGm12878Bclaf101388V0416101PkRep2  0.001796  -0.5678   1.617e-08    GM12878 BCLAF1 v041610.1   
##                                                                                     ChIP-seq Peaks Rep 2 from  
##                                                                                            ENCODE/HAIB         
## 
##  wgEncodeHaibTfbsGm12878Atf2sc81188V0422111PkRep2  0.0007129 -0.2449   1.898e-08     GM12878 ATF2 v042211.1    
##                                                                                     ChIP-seq Peaks Rep 2 from  
##                                                                                            ENCODE/HAIB         
## 
##       wgEncodeHaibTfbsGm12891Pol2Pcr1xPkRep1       0.004814  -0.6803   1.898e-08   GM12891 Pol2 PCR1x ChIP-seq 
##                                                                                   Peaks Rep 1 from ENCODE/HAIB 
## 
##      wgEncodeHaibTfbsGm12878Pou2f2Pcr1xPkRep2      0.003845  -0.6217   2.253e-08  GM12878 POU2F2 PCR1x ChIP-seq
##                                                                                   Peaks Rep 2 from ENCODE/HAIB 
## ---------------------------------------------------------------------------------------------------------------
## 
## [1] "c1 vs. c6 , number of degs significant at adj.p.val<0.5: 66"
## 
## --------------------------------------------------------------------------------------------------------------
##                     Row.names                         c1       c6     adj.P.Val               V2              
## -------------------------------------------------- --------- ------- ----------- -----------------------------
## wgEncodeHaibTfbsGm12878Runx3sc101553V0422111PkRep2 8.939e-05 -0.9353  2.59e-12      GM12878 RUNX3 v042211.1   
##                                                                                    ChIP-seq Peaks Rep 2 from  
##                                                                                           ENCODE/HAIB         
## 
##  wgEncodeHaibTfbsGm12878Pmlsc71910V0422111PkRep2   1.027e-05 -0.9168  3.592e-12      GM12878 PML v042211.1    
##                                                                                    ChIP-seq Peaks Rep 2 from  
##                                                                                           ENCODE/HAIB         
## 
## wgEncodeHaibTfbsGm12878Stat5asc74442V0422111PkRep2 5.806e-05 0.7588   5.061e-11    GM12878 STAT5A v042211.1   
##                                                                                    ChIP-seq Peaks Rep 2 from  
##                                                                                           ENCODE/HAIB         
## 
##  wgEncodeHaibTfbsGm12878Bclaf101388V0416101PkRep2  0.001796  -0.9275  4.125e-10    GM12878 BCLAF1 v041610.1   
##                                                                                    ChIP-seq Peaks Rep 2 from  
##                                                                                           ENCODE/HAIB         
## 
##       wgEncodeHaibTfbsGm12891Pol2Pcr1xPkRep1       0.004814  0.9679   5.483e-10   GM12891 Pol2 PCR1x ChIP-seq 
##                                                                                  Peaks Rep 1 from ENCODE/HAIB 
## 
##      wgEncodeHaibTfbsGm12878Pou2f2Pcr1xPkRep2      0.003845  0.9739   8.288e-10  GM12878 POU2F2 PCR1x ChIP-seq
##                                                                                  Peaks Rep 2 from ENCODE/HAIB 
## 
##  wgEncodeHaibTfbsGm12878Mta3sc81325V0422111PkRep2  7.449e-07 -0.6721  8.288e-10     GM12878 MTA3 v042211.1    
##                                                                                    ChIP-seq Peaks Rep 2 from  
##                                                                                           ENCODE/HAIB         
## 
## wgEncodeHaibTfbsGm12878Stat5asc74442V0422111PkRep1 0.000687  -0.8088  8.414e-10    GM12878 STAT5A v042211.1   
##                                                                                    ChIP-seq Peaks Rep 1 from  
##                                                                                           ENCODE/HAIB         
## 
##  wgEncodeHaibTfbsGm12878Atf2sc81188V0422111PkRep2  0.0007129 -0.8895  2.672e-09     GM12878 ATF2 v042211.1    
##                                                                                    ChIP-seq Peaks Rep 2 from  
##                                                                                           ENCODE/HAIB         
## 
##       wgEncodeHaibTfbsGm12878Pol2Pcr2xPkRep1       0.0001325 0.7987   2.672e-09   GM12878 Pol2 PCR2x ChIP-seq 
##                                                                                  Peaks Rep 1 from ENCODE/HAIB 
## --------------------------------------------------------------------------------------------------------------
## 
## [1] "c2 vs. c3 , number of degs significant at adj.p.val<0.5: 3"
## 
## ----------------------------------------------------------------------------------------------------------
##                    Row.names                       c2        c3      adj.P.Val              V2            
## ------------------------------------------------ ------- ---------- ----------- --------------------------
##    wgEncodeHaibTfbsGm12878Pol24h8Pcr1xPkRep2     0.01412 -0.0009115   0.03041     GM12878 Pol2-4H8 PCR1x  
##                                                                                 ChIP-seq Peaks Rep 2 from 
##                                                                                        ENCODE/HAIB        
## 
## wgEncodeHaibTfbsGm12878Mta3sc81325V0422111PkRep2 0.4086  -0.0008688   0.03113     GM12878 MTA3 v042211.1  
##                                                                                 ChIP-seq Peaks Rep 2 from 
##                                                                                        ENCODE/HAIB        
## 
##   wgEncodeHaibTfbsGm12892Pol24h8V0416102PkRep1   0.1585  -0.004603    0.07884   GM12892 Pol2-4H8 v041610.2
##                                                                                 ChIP-seq Peaks Rep 1 from 
##                                                                                        ENCODE/HAIB        
## ----------------------------------------------------------------------------------------------------------
## 
## [1] "c2 vs. c4 , number of degs significant at adj.p.val<0.5: 11"
## 
## ------------------------------------------------------------------------------------------------------------
##                    Row.names                       c2       c4      adj.P.Val               V2              
## ------------------------------------------------ ------- --------- ----------- -----------------------------
## wgEncodeHaibTfbsHepg2Mybl2sc81192V0422111PkRep2  -0.7955 0.0007234  0.0006506      HepG2 MYBL2 v042211.1    
##                                                                                  ChIP-seq Peaks Rep 2 from  
##                                                                                         ENCODE/HAIB         
## 
## wgEncodeHaibTfbsHepg2Tead4sc101184V0422111PkRep1 -0.9887 0.001973   0.001469       HepG2 TEAD4 v042211.1    
##                                                                                  ChIP-seq Peaks Rep 1 from  
##                                                                                         ENCODE/HAIB         
## 
## wgEncodeHaibTfbsHepg2Mybl2sc81192V0422111PkRep1  -0.9952 0.003229   0.002817       HepG2 MYBL2 v042211.1    
##                                                                                  ChIP-seq Peaks Rep 1 from  
##                                                                                         ENCODE/HAIB         
## 
##  wgEncodeHaibTfbsHepg2Foxa1sc6553V0416101PkRep1  -0.8416 0.006962    0.00499    HepG2 FOXA1 6553 v041610.1  
##                                                                                  ChIP-seq Peaks Rep 1 from  
##                                                                                         ENCODE/HAIB         
## 
##    wgEncodeHaibTfbsHepg2Pol24h8V0416102PkRep1    -0.7936 0.0004534   0.01077     HepG2 Pol2-4H8 v041610.2   
##                                                                                  ChIP-seq Peaks Rep 1 from  
##                                                                                         ENCODE/HAIB         
## 
##        wgEncodeSydhTfbsHepg2Pol2IggrabPk         -0.658  0.000279    0.01197    HEPG2 Pol2 IgG-rab ChIP-seq 
##                                                                                   Peaks from ENCODE/SYDH    
## 
##    wgEncodeHaibTfbsHepg2Pol24h8V0416102PkRep2    -0.5454 1.017e-06   0.01295     HepG2 Pol2-4H8 v041610.2   
##                                                                                  ChIP-seq Peaks Rep 2 from  
##                                                                                         ENCODE/HAIB         
## 
##       wgEncodeHaibTfbsHepg2Pol2Pcr2xPkRep2       0.9687  0.001153    0.01859     HepG2 Pol2 PCR2x ChIP-seq  
##                                                                                Peaks Rep 2 from ENCODE/HAIB 
## 
## wgEncodeHaibTfbsHepg2Mbd4sc271530V0422111PkRep1  -0.8289 0.009568    0.02326   HepG2 MBD4 v042211.1 ChIP-seq
##                                                                                Peaks Rep 1 from ENCODE/HAIB 
## 
##     wgEncodeHaibTfbsHepg2Hey1V0416101PkRep1      -0.9811 0.000285   0.007157                                
## ------------------------------------------------------------------------------------------------------------
## 
## [1] "c3 vs. c4 , number of degs significant at adj.p.val<0.5: 11"
## 
## ------------------------------------------------------------------------------------------------------------
##                    Row.names                       c3       c4      adj.P.Val               V2              
## ------------------------------------------------ ------- --------- ----------- -----------------------------
## wgEncodeHaibTfbsHepg2Mybl2sc81192V0422111PkRep2  0.4549  0.0007234  0.007673       HepG2 MYBL2 v042211.1    
##                                                                                  ChIP-seq Peaks Rep 2 from  
##                                                                                         ENCODE/HAIB         
## 
## wgEncodeHaibTfbsHepg2Mybl2sc81192V0422111PkRep1   -0.86  0.003229   0.009629       HepG2 MYBL2 v042211.1    
##                                                                                  ChIP-seq Peaks Rep 1 from  
##                                                                                         ENCODE/HAIB         
## 
##  wgEncodeHaibTfbsHepg2Foxa1sc6553V0416101PkRep1  -0.9877 0.006962    0.0199     HepG2 FOXA1 6553 v041610.1  
##                                                                                  ChIP-seq Peaks Rep 1 from  
##                                                                                         ENCODE/HAIB         
## 
##    wgEncodeHaibTfbsHepg2Pol24h8V0416102PkRep2    -0.1786 1.017e-06   0.02195     HepG2 Pol2-4H8 v041610.2   
##                                                                                  ChIP-seq Peaks Rep 2 from  
##                                                                                         ENCODE/HAIB         
## 
## wgEncodeHaibTfbsHepg2Tead4sc101184V0422111PkRep1 0.3458  0.001973    0.02195       HepG2 TEAD4 v042211.1    
##                                                                                  ChIP-seq Peaks Rep 1 from  
##                                                                                         ENCODE/HAIB         
## 
##       wgEncodeHaibTfbsHepg2Pol2Pcr2xPkRep2       -0.5218 0.001153    0.02202     HepG2 Pol2 PCR2x ChIP-seq  
##                                                                                Peaks Rep 2 from ENCODE/HAIB 
## 
##        wgEncodeSydhTfbsHepg2Pol2IggrabPk         -0.4535 0.000279    0.02202    HEPG2 Pol2 IgG-rab ChIP-seq 
##                                                                                   Peaks from ENCODE/SYDH    
## 
##    wgEncodeHaibTfbsHepg2Pol24h8V0416102PkRep1    -0.6623 0.0004534   0.02298     HepG2 Pol2-4H8 v041610.2   
##                                                                                  ChIP-seq Peaks Rep 1 from  
##                                                                                         ENCODE/HAIB         
## 
## wgEncodeHaibTfbsHepg2Mbd4sc271530V0422111PkRep1  -0.986  0.009568    0.07367   HepG2 MBD4 v042211.1 ChIP-seq
##                                                                                Peaks Rep 1 from ENCODE/HAIB 
## 
##     wgEncodeHaibTfbsHepg2Hey1V0416101PkRep2      -0.6034 0.003643   0.007673                                
## ------------------------------------------------------------------------------------------------------------
## 
## [1] "c3 vs. c6 , number of degs significant at adj.p.val<0.5: 1"
## 
## ---------------------------------------------------------------------------------------------------------
##                    Row.names                         c3       c6     adj.P.Val             V2            
## ------------------------------------------------ ---------- ------- ----------- -------------------------
## wgEncodeHaibTfbsGm12878Mta3sc81325V0422111PkRep2 -0.0008688 -0.6721   0.04644    GM12878 MTA3 v042211.1  
##                                                                                 ChIP-seq Peaks Rep 2 from
##                                                                                        ENCODE/HAIB       
## ---------------------------------------------------------------------------------------------------------
## 
## [1] "c4 vs. c6 , number of degs significant at adj.p.val<0.5: 11"
## 
## -----------------------------------------------------------------------------------------------------------
##                    Row.names                        c4       c6    adj.P.Val               V2              
## ------------------------------------------------ --------- ------ ----------- -----------------------------
## wgEncodeHaibTfbsHepg2Mybl2sc81192V0422111PkRep2  0.0007234 0.9488  5.268e-05      HepG2 MYBL2 v042211.1    
##                                                                                 ChIP-seq Peaks Rep 2 from  
##                                                                                        ENCODE/HAIB         
## 
## wgEncodeHaibTfbsHepg2Tead4sc101184V0422111PkRep1 0.001973  0.9985  0.0001274      HepG2 TEAD4 v042211.1    
##                                                                                 ChIP-seq Peaks Rep 1 from  
##                                                                                        ENCODE/HAIB         
## 
## wgEncodeHaibTfbsHepg2Mybl2sc81192V0422111PkRep1  0.003229  0.9916  0.0002865      HepG2 MYBL2 v042211.1    
##                                                                                 ChIP-seq Peaks Rep 1 from  
##                                                                                        ENCODE/HAIB         
## 
##  wgEncodeHaibTfbsHepg2Foxa1sc6553V0416101PkRep1  0.006962  0.8901  0.001191    HepG2 FOXA1 6553 v041610.1  
##                                                                                 ChIP-seq Peaks Rep 1 from  
##                                                                                        ENCODE/HAIB         
## 
##    wgEncodeHaibTfbsHepg2Pol24h8V0416102PkRep1    0.0004534 0.6691  0.003514     HepG2 Pol2-4H8 v041610.2   
##                                                                                 ChIP-seq Peaks Rep 1 from  
##                                                                                        ENCODE/HAIB         
## 
##       wgEncodeHaibTfbsHepg2Pol2Pcr2xPkRep2       0.001153  0.6707  0.005071     HepG2 Pol2 PCR2x ChIP-seq  
##                                                                               Peaks Rep 2 from ENCODE/HAIB 
## 
##    wgEncodeHaibTfbsHepg2Pol24h8V0416102PkRep2    1.017e-06 0.4296  0.005513     HepG2 Pol2-4H8 v041610.2   
##                                                                                 ChIP-seq Peaks Rep 2 from  
##                                                                                        ENCODE/HAIB         
## 
## wgEncodeHaibTfbsHepg2Mbd4sc271530V0422111PkRep1  0.009568  0.9875  0.005573   HepG2 MBD4 v042211.1 ChIP-seq
##                                                                               Peaks Rep 1 from ENCODE/HAIB 
## 
##        wgEncodeSydhTfbsHepg2Pol2IggrabPk         0.000279  0.5467  0.005573    HEPG2 Pol2 IgG-rab ChIP-seq 
##                                                                                  Peaks from ENCODE/SYDH    
## 
##     wgEncodeHaibTfbsHepg2Hey1V0416101PkRep1      0.000285  0.7581  0.001305                                
## -----------------------------------------------------------------------------------------------------------
## [1] "Counts of regulatory elements differentially associated with each group"
## 
## --------------------------------------
##  &nbsp;   c1   c2   c3   c4   c5   c6 
## -------- ---- ---- ---- ---- ---- ----
##  **c1**   0    62   65   77   0    66 
## 
##  **c2**   0    0    3    11   0    0  
## 
##  **c3**   0    0    0    11   0    1  
## 
##  **c4**   0    0    0    0    0    11 
## 
##  **c5**   0    0    0    0    0    0  
## 
##  **c6**   0    0    0    0    0    0  
## --------------------------------------

Summary

Now, the same set of diseases is different from the others.

Co-morbidity similarity analysis

We used the data from Hidalgo CA, Blumm N, Barabasi A-L, Christakis NA. PLoS Computational Biology, 5(4):e1000353 doi:10.1371/journal.pcbi.1000353, available at http://barabasilab.neu.edu/projects/hudine/resource/data/data.html. These data provide co-morbidity measurements among pairs of diseases. We map autoimmune disease- and trait names to 3-digits ICD9 codes and evaluate how co-morbidity measurements correlate with regulatory similarity measurements. We used Phi measurement of co-morbidity. The pearson correlation coefficient of Phi and regulatory similarity is:

## [1] 0.3759245

Iridescent literature similarity

## [1] "sharedRels correlation with regulatory similarity"
## [1] 0.3484246
## [1] "obsExp correlation with regulatory similarity"
## [1] 0.5045555
## [1] "minMim correlation with regulatory similarity"
## [1] 0.6470513
## [1] "directStr correlation with regulatory similarity"
## [1] 0.2835723
## [1] "relOverlap correlation with regulatory similarity"
## [1] 0.3602434
## [1] "misn correlation with regulatory similarity"
## [1] 0.672326

UMLS literature similarity

## [1] "msh.path correlation with regulatory similarity"
## [1] 0.2614632
## [1] "snomedct.path correlation with regulatory similarity"
## [1] 0.7064502

Analysis of histone marks

We also performed regulatory similarity analysis using subsets of regulatory datasets, such as Transcription Factor Binding Sites or Histone Modification Marks. Here, out of all regulatory datasets, we selected only Histone marks.

## [1] 721  39
## [1] 610  39

We visualized the matrix of pair-wise pearson correlation coefficients among the term-specific regulatory enrichment profiles.

We then compared how regulatory similarity correlates with shared genomic features similarity. pearson correlation coefficient between the two is:

## [1] 0.6299304

The top 10 pairs of disease-associated SNPs are most similar with each other.

## 
## --------------------------------------------------------------------------
##         Disease 1                  Disease 2            Corr. coefficient 
## ------------------------- ---------------------------- -------------------
##    Multiple_sclerosis     Systemic_lupus_erythematosus       0.6312       
## 
## Primary_biliary_cirrhosis Systemic_lupus_erythematosus       0.5528       
## 
##   Rheumatoid_arthritis         Ulcerative_colitis            0.5467       
## 
##    Multiple_sclerosis      Primary_biliary_cirrhosis         0.4959       
## 
##      HDL_cholesterol            LDL_cholesterol              0.4798       
## 
##     Kawasaki_disease      Systemic_lupus_erythematosus       0.4668       
## 
##    Alzheimers_combined       Restless_legs_syndrome          0.4515       
## 
##      HDL_cholesterol             Triglycerides               0.4354       
## 
##         Psoriasis         Systemic_lupus_erythematosus        0.407       
## 
##      Celiac_disease            Multiple_sclerosis            0.4017       
## --------------------------------------------------------------------------

The regulatory similarity dendrogram can be divided into four separate clusters:

## Cluster01 has   7 members 
## Triglycerides
## Platelet_counts
## Liver_enzyme_levels_gamma_glutamyl_transferase
## HDL_cholesterol
## LDL_cholesterol
## Type_2_diabetes
## Fasting_glucose_related_traits
##  
## Cluster02 has   6 members 
## Celiac_disease
## Multiple_sclerosis
## Primary_biliary_cirrhosis
## Systemic_lupus_erythematosus
## Psoriasis
## Kawasaki_disease
##  
## Cluster03 has  10 members 
## Crohns_disease
## Autoimmune_thyroiditis
## Allergy
## Vitiligo
## Progressive_supranuclear_palsy
## Red_blood_cell_traits
## Ankylosing_spondylitis
## Primary_sclerosing_cholangitis
## Systemic_sclerosis
## Migraine
##  
## Cluster04 has   8 members 
## Alzheimers_combined
## Restless_legs_syndrome
## Atopic_dermatitis
## Bone_mineral_density
## Creatinine_levels
## Chronic_kidney_disease
## Urate_levels
## Renal_function_related_traits_BUN
##  
## Cluster05 has   8 members 
## Type_1_diabetes
## Juvenile_idiopathic_arthritis
## Behcets_disease
## Ulcerative_colitis
## Rheumatoid_arthritis
## Alopecia_areata
## C_reactive_protein
## Asthma
## 

We estimated the differences in regulatory associations of term-secific SNP sets.

The first column shows names of regulatory datasets. The following two columns show the average p-values of the cluster-specific SNP sets-regulatory associations. The smaller a p-value is, the more SNPs in a cluster enriched in corresponsing regulatory dataset. A “-” sign indicates that an association is underrepresented (depleted). The “adj.P.Val” column shows whether a difference in the associations between the clusters is statistically significantly different. The last column shows descriptions of the regulatory datasets. The tables were sorted by “adj.P.Val” column; the top 10 or less most significantly different associations are shown.

## [1] "c1 vs. c2 , number of degs significant at adj.p.val<0.5: 57"
## 
## --------------------------------------------------------------------------------------------------------------
##                    Row.names                        c1        c2      adj.P.Val               V2              
## ----------------------------------------------- ---------- --------- ----------- -----------------------------
## wgEncodeUwHistoneGm12875H3k04me3StdHotspotsRep1  -0.4394   0.0005212  9.005e-07   GM12875 H3K4me3 Histone Mod 
##                                                                                    ChIP-seq Hotspots 1 from   
##                                                                                            ENCODE/UW          
## 
##     wgEncodeBroadHistoneGm12878H3k9acStdPk       -0.01808  3.849e-12  1.828e-06   GM12878 H3K9ac Histone Mods 
##                                                                                     by ChIP-seq Peaks from    
##                                                                                          ENCODE/Broad         
## 
##     wgEncodeBroadHistoneGm12878H3k4me2StdPk     -0.008004  8.782e-09  1.828e-06  GM12878 H3K4me2 Histone Mods 
##                                                                                     by ChIP-seq Peaks from    
##                                                                                          ENCODE/Broad         
## 
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep2   -0.123   5.452e-07  8.189e-06   GM12865 H3K4me3 Histone Mod 
##                                                                                    ChIP-seq Hotspots 2 from   
##                                                                                            ENCODE/UW          
## 
##     wgEncodeBroadHistoneGm12878H3k9me3StdPk     -2.843e-07 2.129e-10  8.189e-06  GM12878 H3K9me3 Histone Mods 
##                                                                                     by ChIP-seq Peaks from    
##                                                                                          ENCODE/Broad         
## 
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep1  -0.1632   2.881e-06  3.078e-05   GM12865 H3K4me3 Histone Mod 
##                                                                                    ChIP-seq Hotspots 1 from   
##                                                                                            ENCODE/UW          
## 
##       wgEncodeBroadHistoneCd20H3k04me2Pk        -0.002374   6.1e-09   3.078e-05  CD20+ H3K4me2 Histone Mods by
##                                                                                       ChIP-seq Peaks from     
##                                                                                          ENCODE/Broad         
## 
##   wgEncodeBroadHistoneGm12878H3k04me3StdPkV2     -0.02222  4.708e-08  3.425e-05  GM12878 H3K4me3 Histone Mods 
##                                                                                     by ChIP-seq Peaks from    
##                                                                                          ENCODE/Broad         
## 
##   wgEncodeBroadHistoneGm12878H3k04me1StdPkV2    -5.857e-05 6.263e-15  3.615e-05  GM12878 H3K4me1 Histone Mods 
##                                                                                     by ChIP-seq Peaks from    
##                                                                                          ENCODE/Broad         
## 
## wgEncodeUwHistoneGm12864H3k04me3StdHotspotsRep2   -0.523   0.003202   3.615e-05   GM12864 H3K4me3 Histone Mod 
##                                                                                    ChIP-seq Hotspots 2 from   
##                                                                                            ENCODE/UW          
## --------------------------------------------------------------------------------------------------------------
## 
## [1] "c1 vs. c3 , number of degs significant at adj.p.val<0.5: 6"
## 
## -------------------------------------------------------------------------------------------------------
##                 Row.names                      c1       c3     adj.P.Val               V2              
## ------------------------------------------ ---------- ------- ----------- -----------------------------
## wgEncodeBroadHistoneA549H3k79me2Dex100nmPk 0.0001024  -0.9021   0.02348     A549 DEX 100 nM H3K79me2   
##                                                                             Histone Mods by ChIP-seq   
##                                                                              Peaks from ENCODE/Broad   
## 
##  wgEncodeBroadHistoneA549H3k79me2Etoh02Pk  0.0002004  0.8357    0.08259     A549 EtOH 0.02% H3K79me2   
##                                                                             Histone Mods by ChIP-seq   
##                                                                              Peaks from ENCODE/Broad   
## 
##     wgEncodeBroadHistoneNhlfH3k79me2Pk     4.751e-05  0.6981    0.08259   NHLF H3K79me2 Histone Mods by
##                                                                                ChIP-seq Peaks from     
##                                                                                   ENCODE/Broad         
## 
##    wgEncodeBroadHistoneHuvecH3k79me2Pk     0.0001697  0.7884    0.08259    HUVEC H3K79me2 Histone Mods 
##                                                                              by ChIP-seq Peaks from    
##                                                                                   ENCODE/Broad         
## 
##     wgEncodeBroadHistoneNhekH3k79me2Pk     0.0001432  0.7962    0.08259   NHEK H3K79me2 Histone Mods by
##                                                                                ChIP-seq Peaks from     
##                                                                                   ENCODE/Broad         
## 
##   wgEncodeBroadHistoneHuvecH3k27me3StdPk   -0.0002469 -0.8449   0.08259    HUVEC H3K27me3 Histone Mods 
##                                                                              by ChIP-seq Peaks from    
##                                                                                   ENCODE/Broad         
## -------------------------------------------------------------------------------------------------------
## 
## [1] "c1 vs. c4 , number of degs significant at adj.p.val<0.5: 34"
## 
## ---------------------------------------------------------------------------------------------------------
##                 Row.names                     c1         c4      adj.P.Val               V2              
## ------------------------------------------ --------- ---------- ----------- -----------------------------
## wgEncodeBroadHistoneA549H3k79me2Dex100nmPk 0.0001024  -0.1158    0.002307     A549 DEX 100 nM H3K79me2   
##                                                                               Histone Mods by ChIP-seq   
##                                                                                Peaks from ENCODE/Broad   
## 
##    wgEncodeBroadHistoneOsteoH4k20me1Pk     0.007273   -0.09496    0.00362   Osteoblasts H4K20me1 Histone 
##                                                                              Mods by ChIP-seq Peaks from 
##                                                                                     ENCODE/Broad         
## 
##     wgEncodeBroadHistoneNhaH4k20me1Pk      0.002923   -0.1011    0.004216   NH-A H4K20me1 Histone Mods by
##                                                                                  ChIP-seq Peaks from     
##                                                                                     ENCODE/Broad         
## 
##     wgEncodeBroadHistoneNhekH3k79me2Pk     0.0001432  -0.07455   0.006329   NHEK H3K79me2 Histone Mods by
##                                                                                  ChIP-seq Peaks from     
##                                                                                     ENCODE/Broad         
## 
##  wgEncodeBroadHistoneA549H3k79me2Etoh02Pk  0.0002004  -0.2685    0.009682     A549 EtOH 0.02% H3K79me2   
##                                                                               Histone Mods by ChIP-seq   
##                                                                                Peaks from ENCODE/Broad   
## 
##  wgEncodeBroadHistoneNhdfadH3k36me3StdPk    0.04191  -0.005215    0.0131    NHDF-Ad H3K36me3 Histone Mods
##                                                                                by ChIP-seq Peaks from    
##                                                                                     ENCODE/Broad         
## 
##    wgEncodeBroadHistoneHuvecH3k79me2Pk     0.0001697  -0.3014     0.0131     HUVEC H3K79me2 Histone Mods 
##                                                                                by ChIP-seq Peaks from    
##                                                                                     ENCODE/Broad         
## 
##   wgEncodeBroadHistoneNhekH3k36me3StdPk    0.002936   -0.02459    0.01416   NHEK H3K36me3 Histone Mods by
##                                                                                  ChIP-seq Peaks from     
##                                                                                     ENCODE/Broad         
## 
##   wgEncodeBroadHistoneHmecH3k36me3StdPk    0.001914  -0.0002847   0.01711   HMEC H3K36me3 Histone Mods by
##                                                                                  ChIP-seq Peaks from     
##                                                                                     ENCODE/Broad         
## 
##     wgEncodeBroadHistoneNhlfH3k79me2Pk     4.751e-05  -0.6816     0.02063   NHLF H3K79me2 Histone Mods by
##                                                                                  ChIP-seq Peaks from     
##                                                                                     ENCODE/Broad         
## ---------------------------------------------------------------------------------------------------------
## 
## [1] "c1 vs. c5 , number of degs significant at adj.p.val<0.5: 57"
## 
## ---------------------------------------------------------------------------------------------------------
##                 Row.names                      c1        c5      adj.P.Val               V2              
## ------------------------------------------ ---------- --------- ----------- -----------------------------
## wgEncodeBroadHistoneA549H3k79me2Dex100nmPk 0.0001024  -0.007415  4.128e-05    A549 DEX 100 nM H3K79me2   
##                                                                               Histone Mods by ChIP-seq   
##                                                                                Peaks from ENCODE/Broad   
## 
##  wgEncodeBroadHistoneA549H3k79me2Etoh02Pk  0.0002004   -0.0104   0.0003534    A549 EtOH 0.02% H3K79me2   
##                                                                               Histone Mods by ChIP-seq   
##                                                                                Peaks from ENCODE/Broad   
## 
##     wgEncodeBroadHistoneNhaH3k79me2Pk      0.0009854  -0.002468  0.0004093  NH-A H3K79me2 Histone Mods by
##                                                                                  ChIP-seq Peaks from     
##                                                                                     ENCODE/Broad         
## 
##    wgEncodeBroadHistoneHuvecH3k79me2Pk     0.0001697   -0.0123   0.0004093   HUVEC H3K79me2 Histone Mods 
##                                                                                by ChIP-seq Peaks from    
##                                                                                     ENCODE/Broad         
## 
##    wgEncodeBroadHistoneOsteoH3k79me2Pk      0.002415  -0.004605  0.0004484  Osteoblasts H3K79me2 Histone 
##                                                                              Mods by ChIP-seq Peaks from 
##                                                                                     ENCODE/Broad         
## 
##     wgEncodeBroadHistoneNhlfH3k79me2Pk     4.751e-05  -0.01706   0.0006228  NHLF H3K79me2 Histone Mods by
##                                                                                  ChIP-seq Peaks from     
##                                                                                     ENCODE/Broad         
## 
##   wgEncodeBroadHistoneHuvecH3k27me3StdPk   -0.0002469  0.01744   0.0006936   HUVEC H3K27me3 Histone Mods 
##                                                                                by ChIP-seq Peaks from    
##                                                                                     ENCODE/Broad         
## 
##   wgEncodeBroadHistoneHsmmH3k79me2StdPk    0.0006338   -0.0148   0.0006936  HSMM H3K79me2 Histone Mods by
##                                                                                  ChIP-seq Peaks from     
##                                                                                     ENCODE/Broad         
## 
##     wgEncodeBroadHistoneNhekH3k79me2Pk     0.0001432  -0.02136   0.0006936  NHEK H3K79me2 Histone Mods by
##                                                                                  ChIP-seq Peaks from     
##                                                                                     ENCODE/Broad         
## 
##   wgEncodeBroadHistoneHsmmH3k27me3StdPk    -0.001048  1.409e-09  0.0008928  HSMM H3K27me3 Histone Mods by
##                                                                                  ChIP-seq Peaks from     
##                                                                                     ENCODE/Broad         
## ---------------------------------------------------------------------------------------------------------
## 
## [1] "c2 vs. c3 , number of degs significant at adj.p.val<0.5: 37"
## 
## -----------------------------------------------------------------------------------------------------------
##                    Row.names                       c2       c3     adj.P.Val               V2              
## ----------------------------------------------- --------- ------- ----------- -----------------------------
## wgEncodeUwHistoneGm12875H3k04me3StdHotspotsRep1 0.0005212 -0.8239  9.755e-07   GM12875 H3K4me3 Histone Mod 
##                                                                                 ChIP-seq Hotspots 1 from   
##                                                                                         ENCODE/UW          
## 
##     wgEncodeBroadHistoneGm12878H3k9acStdPk      3.849e-12 0.5541   1.714e-05   GM12878 H3K9ac Histone Mods 
##                                                                                  by ChIP-seq Peaks from    
##                                                                                       ENCODE/Broad         
## 
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep2 5.452e-07 -0.8528  2.26e-05    GM12865 H3K4me3 Histone Mod 
##                                                                                 ChIP-seq Hotspots 2 from   
##                                                                                         ENCODE/UW          
## 
##     wgEncodeBroadHistoneGm12878H3k4me2StdPk     8.782e-09 -0.6556  2.26e-05   GM12878 H3K4me2 Histone Mods 
##                                                                                  by ChIP-seq Peaks from    
##                                                                                       ENCODE/Broad         
## 
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep1 2.881e-06 -0.9392  0.0001006   GM12865 H3K4me3 Histone Mod 
##                                                                                 ChIP-seq Hotspots 1 from   
##                                                                                         ENCODE/UW          
## 
## wgEncodeUwHistoneGm12864H3k04me3StdHotspotsRep2 0.003202  -0.9901  0.0001157   GM12864 H3K4me3 Histone Mod 
##                                                                                 ChIP-seq Hotspots 2 from   
##                                                                                         ENCODE/UW          
## 
##    wgEncodeBroadHistoneGm12878H3k79me2StdPk     1.867e-08 -0.8139  0.0001487  GM12878 H3K79me2 Histone Mods
##                                                                                  by ChIP-seq Peaks from    
##                                                                                       ENCODE/Broad         
## 
##       wgEncodeBroadHistoneDnd41H3k09acPk        0.0001527 0.7596   0.0001965  Dnd41 H3K9ac Histone Mods by 
##                                                                                    ChIP-seq Peaks from     
##                                                                                       ENCODE/Broad         
## 
##       wgEncodeBroadHistoneDnd41H3k04me1Pk       9.105e-08 0.7344   0.0003011  Dnd41 H3K4me1 Histone Mods by
##                                                                                    ChIP-seq Peaks from     
##                                                                                       ENCODE/Broad         
## 
##   wgEncodeBroadHistoneGm12878H3k04me3StdPkV2    4.708e-08 0.7527   0.0003011  GM12878 H3K4me3 Histone Mods 
##                                                                                  by ChIP-seq Peaks from    
##                                                                                       ENCODE/Broad         
## -----------------------------------------------------------------------------------------------------------
## 
## [1] "c2 vs. c4 , number of degs significant at adj.p.val<0.5: 56"
## 
## --------------------------------------------------------------------------------------------------------------
##                    Row.names                       c2         c4      adj.P.Val               V2              
## ----------------------------------------------- --------- ---------- ----------- -----------------------------
## wgEncodeUwHistoneGm12875H3k04me3StdHotspotsRep1 0.0005212  -0.3919    3.243e-07   GM12875 H3K4me3 Histone Mod 
##                                                                                    ChIP-seq Hotspots 1 from   
##                                                                                            ENCODE/UW          
## 
##     wgEncodeBroadHistoneGm12878H3k4me2StdPk     8.782e-09  -0.02811   3.964e-06  GM12878 H3K4me2 Histone Mods 
##                                                                                     by ChIP-seq Peaks from    
##                                                                                          ENCODE/Broad         
## 
##     wgEncodeBroadHistoneGm12878H3k9acStdPk      3.849e-12  -0.1383    3.964e-06   GM12878 H3K9ac Histone Mods 
##                                                                                     by ChIP-seq Peaks from    
##                                                                                          ENCODE/Broad         
## 
##    wgEncodeBroadHistoneGm12878H3k79me2StdPk     1.867e-08 -0.005656   7.731e-06  GM12878 H3K79me2 Histone Mods
##                                                                                     by ChIP-seq Peaks from    
##                                                                                          ENCODE/Broad         
## 
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep2 5.452e-07  -0.2947    1.082e-05   GM12865 H3K4me3 Histone Mod 
##                                                                                    ChIP-seq Hotspots 2 from   
##                                                                                            ENCODE/UW          
## 
##   wgEncodeBroadHistoneGm12878H3k04me3StdPkV2    4.708e-08  -0.01621   2.189e-05  GM12878 H3K4me3 Histone Mods 
##                                                                                     by ChIP-seq Peaks from    
##                                                                                          ENCODE/Broad         
## 
##     wgEncodeBroadHistoneGm12878H3k9me3StdPk     2.129e-10 -1.413e-05  2.824e-05  GM12878 H3K9me3 Histone Mods 
##                                                                                     by ChIP-seq Peaks from    
##                                                                                          ENCODE/Broad         
## 
## wgEncodeUwHistoneGm12864H3k04me3StdHotspotsRep2 0.003202   -0.5261    2.824e-05   GM12864 H3K4me3 Histone Mod 
##                                                                                    ChIP-seq Hotspots 2 from   
##                                                                                            ENCODE/UW          
## 
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep1 2.881e-06  -0.3212    2.824e-05   GM12865 H3K4me3 Histone Mod 
##                                                                                    ChIP-seq Hotspots 1 from   
##                                                                                            ENCODE/UW          
## 
##       wgEncodeBroadHistoneDnd41H3k09acPk        0.0001527  -0.3194    2.824e-05  Dnd41 H3K9ac Histone Mods by 
##                                                                                       ChIP-seq Peaks from     
##                                                                                          ENCODE/Broad         
## --------------------------------------------------------------------------------------------------------------
## 
## [1] "c2 vs. c5 , number of degs significant at adj.p.val<0.5: 64"
## 
## -----------------------------------------------------------------------------------------------------------
##                    Row.names                       c2       c5     adj.P.Val               V2              
## ----------------------------------------------- --------- ------- ----------- -----------------------------
## wgEncodeUwHistoneGm12875H3k04me3StdHotspotsRep1 0.0005212 0.7538   1.095e-05   GM12875 H3K4me3 Histone Mod 
##                                                                                 ChIP-seq Hotspots 1 from   
##                                                                                         ENCODE/UW          
## 
##     wgEncodeBroadHistoneGm12878H3k9acStdPk      3.849e-12 0.1729   0.0001041   GM12878 H3K9ac Histone Mods 
##                                                                                  by ChIP-seq Peaks from    
##                                                                                       ENCODE/Broad         
## 
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep2 5.452e-07 0.5657   0.0001705   GM12865 H3K4me3 Histone Mod 
##                                                                                 ChIP-seq Hotspots 2 from   
##                                                                                         ENCODE/UW          
## 
##     wgEncodeBroadHistoneGm12878H3k4me2StdPk     8.782e-09 0.4824   0.0001705  GM12878 H3K4me2 Histone Mods 
##                                                                                  by ChIP-seq Peaks from    
##                                                                                       ENCODE/Broad         
## 
##       wgEncodeBroadHistoneDnd41H3k09acPk        0.0001527 -0.7471  0.0002681  Dnd41 H3K9ac Histone Mods by 
##                                                                                    ChIP-seq Peaks from     
##                                                                                       ENCODE/Broad         
## 
##    wgEncodeBroadHistoneGm12878H3k79me2StdPk     1.867e-08 -0.4384  0.0002681  GM12878 H3K79me2 Histone Mods
##                                                                                  by ChIP-seq Peaks from    
##                                                                                       ENCODE/Broad         
## 
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep1 2.881e-06 0.7265   0.0002681   GM12865 H3K4me3 Histone Mod 
##                                                                                 ChIP-seq Hotspots 1 from   
##                                                                                         ENCODE/UW          
## 
## wgEncodeUwHistoneGm12864H3k04me3StdHotspotsRep2 0.003202  0.8722   0.0002936   GM12864 H3K4me3 Histone Mod 
##                                                                                 ChIP-seq Hotspots 2 from   
##                                                                                         ENCODE/UW          
## 
##       wgEncodeBroadHistoneDnd41H3k04me1Pk       9.105e-08 -0.5579  0.0003657  Dnd41 H3K4me1 Histone Mods by
##                                                                                    ChIP-seq Peaks from     
##                                                                                       ENCODE/Broad         
## 
##       wgEncodeBroadHistoneCd20H3k04me2Pk         6.1e-09  -0.3652  0.0005895  CD20+ H3K4me2 Histone Mods by
##                                                                                    ChIP-seq Peaks from     
##                                                                                       ENCODE/Broad         
## -----------------------------------------------------------------------------------------------------------
## 
## [1] "c3 vs. c5 , number of degs significant at adj.p.val<0.5: 3"
## 
## -------------------------------------------------------------------------------------------------------
##                 Row.names                    c3        c5      adj.P.Val               V2              
## ------------------------------------------ ------- ---------- ----------- -----------------------------
##   wgEncodeBroadHistoneHsmmH3k27me3StdPk    -0.6298 1.409e-09    0.06695   HSMM H3K27me3 Histone Mods by
##                                                                                ChIP-seq Peaks from     
##                                                                                   ENCODE/Broad         
## 
##    wgEncodeBroadHistoneDnd41Ezh239875Pk    -0.253  0.0006476    0.06695    Dnd41 EZH2 (39875) Histone  
##                                                                            Mods by ChIP-seq Peaks from 
##                                                                                   ENCODE/Broad         
## 
## wgEncodeBroadHistoneA549H3k36me3Dex100nmPk 0.08468 -0.0008403   0.08249     A549 DEX 100 nM H3K36me3   
##                                                                             Histone Mods by ChIP-seq   
##                                                                              Peaks from ENCODE/Broad   
## -------------------------------------------------------------------------------------------------------
## 
## [1] "c4 vs. c5 , number of degs significant at adj.p.val<0.5: 2"
## 
## --------------------------------------------------------------------------------------------------
##               Row.names                  c4       c5      adj.P.Val               V2              
## ------------------------------------- -------- --------- ----------- -----------------------------
## wgEncodeBroadHistoneHsmmH3k27me3StdPk -0.02171 1.409e-09   0.0213    HSMM H3K27me3 Histone Mods by
##                                                                           ChIP-seq Peaks from     
##                                                                              ENCODE/Broad         
## 
##  wgEncodeBroadHistoneNhekEzh239875Pk  -0.1117  0.009518    0.0213      NHEK EZH2 (39875) Histone  
##                                                                       Mods by ChIP-seq Peaks from 
##                                                                              ENCODE/Broad         
## --------------------------------------------------------------------------------------------------
## [1] "Counts of regulatory elements differentially associated with each group"
## 
## ---------------------------------
##  &nbsp;   c1   c2   c3   c4   c5 
## -------- ---- ---- ---- ---- ----
##  **c1**   0    57   6    34   57 
## 
##  **c2**   0    0    37   56   64 
## 
##  **c3**   0    0    0    0    3  
## 
##  **c4**   0    0    0    0    2  
## 
##  **c5**   0    0    0    0    0  
## ---------------------------------

Summary

Co-morbidity similarity analysis

We used the data from Hidalgo CA, Blumm N, Barabasi A-L, Christakis NA. PLoS Computational Biology, 5(4):e1000353 doi:10.1371/journal.pcbi.1000353, available at http://barabasilab.neu.edu/projects/hudine/resource/data/data.html. These data provide co-morbidity measurements among pairs of diseases. We map autoimmune disease- and trait names to 3-digits ICD9 codes and evaluate how co-morbidity measurements correlate with regulatory similarity measurements. We used Phi measurement of co-morbidity. The pearson correlation coefficient of Phi and regulatory similarity is:

## [1] 0.3799314

Iridescent literature similarity

## [1] "sharedRels correlation with regulatory similarity"
## [1] 0.3395089
## [1] "obsExp correlation with regulatory similarity"
## [1] 0.5154583
## [1] "minMim correlation with regulatory similarity"
## [1] 0.6535677
## [1] "directStr correlation with regulatory similarity"
## [1] 0.1748984
## [1] "relOverlap correlation with regulatory similarity"
## [1] 0.3594159
## [1] "misn correlation with regulatory similarity"
## [1] 0.6776696

UMLS literature similarity

## [1] "msh.path correlation with regulatory similarity"
## [1] 0.2743516
## [1] "snomedct.path correlation with regulatory similarity"
## [1] 0.7275952

Misc

Distribution of maxMin correlation coefficients